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Staphylococcus pseudintermedius 5'-nucleotidase suppresses canine phagocytic activity.
Veterinary Microbiology ( IF 2.4 ) Pub Date : 2020-05-16 , DOI: 10.1016/j.vetmic.2020.108720
Mohamed A Abouelkhair 1 , Linda A Frank 2 , David A Bemis 3 , Richard J Giannone 4 , Stephen A Kania 3
Affiliation  

Staphylococcus pseudintermedius is a major opportunistic bacterial pathogen and the leading cause of pyoderma in dogs. In canines it is also often associated with infections of the urinary system and wounds and occasionally infects people. Widespread antimicrobial resistance has made the development of alternative treatments a high priority. The development of a staphylococcal vaccine, however, has proven challenging. Identification of virulence factors that inhibit phagocytosis and avoid innate immunity may play a significant role in preventing or treating infection with S. pseudintermedius. In this study, we identified a putative 5′-nucleotidase provisionally named SpAdsA, a S. pseudintermedius cell- wall protein encoded by SpAdsA. SpAdsA shares approximately 52% identity with the orthologous protein of Staphylococcus aureus and 14.8% identity with that of Streptococcus suis type2. It catalyzes the dephosphorylation of adenosine triphosphate and attenuation of this enzyme with critical amino acid substitutions nearly eliminated its hydrolytic activity. Exogenous adenosine inhibited phagocytosis of S. pseudintermedius by canine neutrophils and monocytes. Conversely, the addition of SpAdsA inhibitor or A2A adenosine receptor antagonist impaired the capacity of S. pseudintermedius to escape from killing by phagocytic cells. The neutralizing ability of canine antibody produced against SpAdsA-M was determined. Taken together, these results suggest that SpAdsA likely plays an important role in S. pseudintermedius virulence and that attenuated SpAdsA may be a good candidate for inclusion in a vaccine against S. pseudintermedius.



中文翻译:

金黄色葡萄球菌5'-核苷酸酶抑制犬的吞噬活性。

金黄色葡萄球菌是一种主要的机会细菌病原体,是犬脓皮病的主要原因。在犬中,它通常还与泌尿系统和伤口的感染有关,并偶尔感染人。广泛的抗药性使替代疗法的开发成为当务之急。然而,事实证明,葡萄球菌疫苗的开发具有挑战性。鉴定抑制吞噬作用并避免先天免疫的毒力因子可能在预防或治疗假单胞菌感染中起重要作用。在这项研究中,我们鉴定了一个暂定名为SpAdsA的5'核苷酸酶,SpAdsA是SpAdsA编码的假单胞菌细胞壁蛋白。SpAdsA与金黄色葡萄球菌的直系同源蛋白质具有大约52%的同一性,与2猪链球菌具有14.8%的同一性。它催化三磷酸腺苷的去磷酸化,并且该酶被关键的氨基酸取代减弱后几乎消除了其水解活性。外源性腺苷抑制犬嗜中性粒细胞和单核细胞吞噬假丝酵母。相反,添加SpAdsA抑制剂或A 2A腺苷受体拮抗剂会损害假丝酵母的能力逃脱吞噬细胞的杀伤。测定了产生的针对SpAdsA-M的犬抗体的中和能力。综上所述,这些结果表明SpAdsA可能在伪中间链霉菌的毒力中起重要作用,并且减毒的SpAdsA可能是包含在抗伪中间链霉菌疫苗中的良好候选

更新日期:2020-05-16
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